CD94/NKG2A is a cytotoxicity inhibitory receptor found on subsets of NK, NKT and T cells, which restricts their killing of cells expressing the CD94/NKG2A-ligand HLA-E (see, e.g., WO99/28748). Antibodies that inhibit CD94/NKG2A may increase the cytolytic activity of tumor-specific lymphocytes against tumor cells. Therefore, therapeutic antibodies that inhibit CD94/NKG2A in cancer patients without killing CD94/NKG2A-expressing cells may be able to control tumor-growth. In addition, certain lymphomas such as, e.g., NK-lymphomas, are characterized by CD94/NKG2A expression. In such patients, therapeutic antibodies that target and kill CD94/NKG2A-expressing cells may be able to eradicate tumor cells. Anti-NKG2A antibodies have also been suggested for use in treating autoimmune or inflammatory diseases (see, e.g., US20030095965A1, WO2006070286).
Various antibodies against CD94/NKG2A have been described in the art. For example, Sivori et al. (Eur J Immunol 1996; 26:2487-92) refers to the murine anti-NKG2A antibody Z270; Carretero et al. (Eur J Immunol 1997; 27:563-7) describes murine anti-NKG2A antibody Z199 (now commercially available via Beckman Coulter, Inc., Product No. IM2750, USA); Vance et al. (J Exp Med 1999; 190: 1801-12) refers to murine anti-NKG2-antibody 20D5 (now commercially available via BD Biosciences Pharmingen, Catalog No. 550518, USA); and U.S. patent application publication 20030095965 describes murine antibody 3S9, which purportedly binds to NKG2A, NKG2C and NKG2E.
Currently available anti-CD94/NKG2A antibodies are of non-human origin, which makes them unsuitable for most therapeutic applications in humans due to their immunogenicity. While simple humanization approaches such as, e.g., CDR-grafting, are available, individualized humanization approaches are typically needed to obtain an optimal humanized variant, minimizing immunogenicity while sufficiently retaining or improving functional properties. Accordingly, there is a need for anti-CD94/NKG2A antibodies that are suitable for treatment of human patients.